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H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 253 records · Page 14Linked to original sources
PubMed1991

[A mechanism of usefulness of treatment with erythromycin for diffuse panbronchiolitis].

The clinical usefulness of treatment with erythromycin for diffuse panbronchiolitis (DPB) patients have been well reported to date, although its mechanisms remain unknown. In a previous study, we demonstrated that DPB patients were found to have large percentages of neutrophils in their lower respiratory tracts and suggested that neutrophils play an important role in the pathogenesis of DPB (Chest 99: 917-923, 1990). While in vitro and in vivo studies have demonstrated that erythromycin decreases neutrophils directed migration. In the present study, we performed bronchoalveolar lavage (BAL) on eight patients with DPB to clarify the cell populations in the lower respiratory tract before and after treatment with erythromycin. Neutrophils percentages in BAL fluid were significantly reduced after treatment with erythromycin (54.3 +/- 22.4% to 13.1 +/- 13.5%, p less than 0.01). No significant variance of BAL lymphocyte percentages was demonstrated after treatment with erythromycin. These results suggest that a main mechanism of clinical usefulness of treatment with erythromycin for DPB may be inhibition of neutrophils migration into the lower respiratory tract instead of intrapulmonary bactericidal activity against organisms.

Adolescent↗
PubMed1991

[Elastase activity in bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis].

The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden.

Adolescent↗
PubMed1991

Reassessment of [3H]glutamate binding to human brain membrane preparations.

We studied [3H]glutamate binding to human brain membrane preparations. We found that the binding assay of [3H]glutamate should be done at 4 degrees C using glass-fiber filters pretreated with polyethyleneimine, sterile incubation buffer, and membrane preparations pretreated with a detergent. Under these assay conditions, we have characterized the three subtypes of glutamate receptors: N-methyl-D-aspartate-, quisqualate- and kainate-sensitive binding sites. Scatchard analysis revealed that the N-methyl-D-aspartate-sensitive [3H]glutamate binding sites consisted of a single component with a dissociation constant (Kd) of 28.2 +/- 2.8 nM and total concentration (Bmax) of 36.2 +/- 3.6 fmol/mg protein (N = 8). These data were much different from those presented in previous studies.

Aged↗
PubMed1991

Epithio-11,12-methano-thromboxane A2 stimulates inositol phosphates accumulation in isolated canine mesenteric artery strips.

Epithio-11,12-methano-thromboxane A2 (STA2), a stable analog of thromboxane A2 (TXA2), stimulated inositol phosphates (IPs) accumulation in canine mesenteric artery strips, but not in cerebral (basilar) artery strips. When canine mesenteric artery strips were incubated with 0.1 microM [3H]myo-inositol for 15 min and then stimulated with 10 microM STA2 for 30 min, there was a significant increase in 3H-IPs accumulation as measured by anion exchange chromatography (2,028 +/- 204 and 3,526 +/- 210* dpm/mg protein for basal and stimulated accumulations, respectively; means +/- S.E.M., n = 3, *P less than 0.01, significantly different from the basal value). This effect of STA2 was dose-dependent with an EC50 value of 1.6 +/- 0.2 microM. The presence of equimolar concentrations of TXA2 receptor antagonists, either ONO-3708 (9,11-dimethylmethano-11,12-methano-13,14-dihydro-13-aza-14-oxo-15 -cyclopental- 16,17,18,19,20-pentanor-15-epi-thromboxane A2) or S-1452 (5Z-7-(3-endo-phenylsulfonylamino-(2.2.1)-bicyclohept- 2-exo-yl)heptenoic acid), completely blocked the effect of STA2. These results suggest the presence of TXA2 receptors coupled with IPs accumulation in canine mesenteric artery strips. The exact location of the TXA2 receptor-IPs system, however, remains unknown.

Animals↗
PubMed1991

[Paroxysmal nocturnal hemoglobinuria (PNH) deficiency of major complement-regulatory membrane proteins on erythrocytes].

The significance of the deficiency of the major complement-regulatory membrane proteins, decay-accelerating factor (DAF) and CD59, to the lysis of paroxysmal nocturnal hemoglobinuria (PNH) red blood cells was investigated. DAF and CD59 were demonstrated to be deficient simultaneously on affected PNH red blood cells (PNH-III) by two-color FACS analysis. At least in some patients with PNH, PNH-I was also revealed to be deficient partially in DAF. Purified DAF and CD59 ameliorated the complement sensitivity of PNH red blood cells, partially and completely, respectively. Functional blocking of these molecules on nomrla human red cells by monoclonal antibodies to DAF and CD59 rendered A or AB type blood cells complement-sensitive but not O or B blood type blood cells. The differences of complement-sensitivity among blood types were revealed to reside on the step of binding of C9 to C5b-8, i. e. C9 can bind to C5b-8 more on A type blood cells than on O type blood cells. We conclude that the deficiency of DAF and CD59 play a major role for the complement sensitivity of PNH red blood cells and that other factors reported to be deficient in PNH do less than these two proteins.

Antigens, CD↗
PubMed1991

[Endothelin-1 induced relaxation of guinea pig trachea after an anaphylactic reaction].

Endothelin-1 (ET-1), one of the most potent constrictors of airway smooth muscles, is reported to act on such inflammatory cells as mast cells and release several chemical mediators. We observed a transient relaxation response to ET-1 after an anaphylactic constriction of guinea pig tracheal smooth muscle. The guinea pig was actively sensitized with ovalbumin, and the tracheal strip was challenged with ovalbumin in vitro. ET-1 induced a transient relaxation followed by a constriction of the tracheal strip. The potency of the relaxation induced by 10(-9) M of ET-1 was 16.0 +/- 1.3%, compared to the response to isoproterenol (2 x 10(-5) M), and the duration of the relaxation was 7.2 +/- 0.7 minutes. Indomethacin (10(-6) M) had no effect on the response, indicated that prostaglandins have no relation. Mechanical denudation of the tracheal epithelium did not reduce the relaxation, but rather augmented it. These results indicate that ET-1 induces a relaxation, associated with a relaxation factor from non-epithelial tissue.

Anaphylaxis↗
PubMed1990

Changes in signal transduction in Alzheimer's disease.

We studied the signal transduction system including the receptor and protein kinase C (PKC) in Alzheimer's disease (AD) brains. We used 3H-TCP as a ligand for the NMDA receptor-ion channel complex. The total concentrations of 3H-TCP binding sites were significantly reduced in AD frontal cortex. 3H-TCP binding sites spared in AD brains retained the affinity for the ligand and the reactivity to NMDA, L-glutamate, and glycine. We utilized antibodies to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC (beta II) was lower in AD particulate fractions and higher in AD cytosol fractions. Immunocytochemical studies revealed reduced numbers of anti-PKC (beta II)-immunopositive neurons. Anti-PKC (alpha) faintly stained entire plaques and surrounding glial cells. Anti-PKC (beta I) stained dystrophic plaque neurites. Anti-PKC (beta II) stained the amyloid-containing portions of plaques. These results suggest an involvement of second messenger cascades in the pathogenesis of AD in addition to neurotransmitters and their receptors.

Aged↗
PubMed1990

Biomodulator-mediated susceptibility of endogenous lipid droplets from rat adipocytes to hormone-sensitive lipase.

The amount of fatty acid release by a fat cell homogenate without pretreatment with epinephrine was found to be slightly more than that released from fat cells by epinephrine, suggesting that fat cells contain high lipolytic activity even in the absence of lipolytic agents. Fat cells contain high hormone-sensitive lipase activity (1383 mumole free fatty acids/g/hr) in the absence of epinephrine, and addition of epinephrine to the cells did not increase the activity, significantly. Like epinephrine, DBcAMP and/or theophylline also elicited marked release of glycerol from fat cells without activating the hormone-sensitive lipase activity. However, although fat cells contain a large amount of hormone-sensitive lipase, lipolysis was negligible in the absence of these lipolytic agents. These results suggest that lipolytic agents such as epinephrine, DBcAMP, and theophylline induce lipolysis in fat cells through some mechanism other than activation of hormone-sensitive lipase and that in the absence of lipolytic agents, some system in fat cells inhibits lipolysis of endogenous lipid droplets by hormone-sensitive lipase. The lipid droplets in fat cells consist mainly of triglyceride with phospholipids, cholesterol, carbohydrate, and protein as minor constituents. The phospholipid fraction was found to consist of 75% phosphatidylcholine and 25% phosphatidylethanolamine. Of the minor constituents of endogenous lipid droplets, only phosphatidylcholine strongly inhibited hormone-sensitive lipase activity in a [3H]triolein emulsion. These results suggest that phosphatidylcholine in endogenous lipid droplets may be responsible for inhibition of hormone-sensitive lipase. Then, a cell-free system was established in which epinephrine, DBcAMP, and theophylline stimulated lipolysis of endogenous lipid droplets from fat cells by lipase solution. In this system, these lipolytic agents did not induce lipolysis in the absence of added lipase. Lipolysis in the mixture of the endogenous lipid droplets and lipase solution was accelerated by phospholipase C with concomitant loss of epinephrine-induced lipolysis. After pretreatment of the endogenous lipid droplets with phospholipase C, these lipolytic agents no longer induced lipolysis. Pretreatment of the endogenous lipid droplets with phospholipase C reduced their phospholipid content with the formation of phosphorylcholine, but did not affect their triglyceride and cholesterol contents. Treatment of the endogenous lipid droplets with phospholipase D did not affect lipolysis in the cell-free system. These results suggest that phosphatidylcholine in the endogenous lipid droplets may inhibit their lipolysis by hormone-sensitive lipase in fat cells and also be involved in the mechanisms of the stimulatory effects of epinephrine, DBcAMP, and theophylline on lipolysis.

Adipose Tissue↗
PubMed1990

Deficiency of glycosyl-phosphatidylinositol anchored proteins on paroxysmal nocturnal haemoglobinuria (PNH) neutrophils and monocytes: heterogeneous deficiency of decay-accelerating factor (DAF) and CD16 on PNH neutrophils.

Glycosyl-phosphatidylinositol (GPI) anchored membrane proteins have been reported to be deficient on affected paroxysmal nocturnal haemoglobinuria (PNH) blood cells. In the present study we investigated the deficiency of several GPI anchored membrane proteins on PNH neutrophils (PMN) and monocytes from 10 patients with PNH. Decay-accelerating factor (DAF) and Fc gamma R-III (CD16) on PMN, DAF and CD14 on monocytes, were investigated by two-colour immunofluorocytometry. Neutrophil alkaline phosphatase activity was also assayed on PNH neutrophils. Normal human PMN were always shown phenotypically to be DAF+/CD16+. A DAF-/CD16- subpopulation of PMN was demonstrated in all the patients studied. In six out of the 10 patients, deficiencies of DAF and CD16 were found simultaneously on affected PNH PMN. The percentage of DAF- PMN showed a positive correlation with the neutrophil alkaline phosphatase (NAP) score. However, it should be noted that, in four out of the 10 patients with PNH, a DAF+/CD16- subpopulation of PMN was also clearly found. This may indicate that the deficiencies of DAF and CD16 on PNH PMN are heterogeneous. Normal human monocytes were demonstrated to be DAF+/CD14+, whereas PNH monocytes consisted of subpopulations of DAF+/CD14+ and DAF-/CD14-. In the same patients with PNH, the deficiencies of DAF on PMN and monocytes correlated well with each other. These results suggest that, at least in some patients with PNH, the mechanisms which induce the membrane defects of PNH blood cells are heterogeneous.

Adult↗
PubMed1990

Enhanced complement-susceptibility and dysfunction of lymphocytes in paroxysmal nocturnal haemoglobinuria (PNH).

We investigated the complement-susceptibility of paroxysmal nocturnal haemoglobinuria (PNH) lymphocytes in relation to their dysfunction. When assessed by complement-mediated lysis induced by monoclonal antibodies (CD5 or CD20) and rabbit complement, the complement-susceptibility of lymphocytes from patients with PNH, both CD5+ (T cells) and CD20+ (B cells), was greater than that from controls (P less than 0.001). This susceptibility was further enhanced, both in normal controls (P less than 0.01) and in patients with PNH (P less than 0.001), when the activity of decay-accelerating factor (DAF) on the lymphocytes was blocked with anti-DAF monoclonal antibody. DAF amounts in mononuclear cells (MNC) from patients with PNH, measured by an enzyme-linked immunosorbent assay (ELISA), were lower than those of the controls (P less than 0.001). The expressions of DAF on T cells and on B cells from patients with PNH were significantly decreased (P less than 0.05 in T cells: P less than 0.01 in B cells). MNC from patients with PNH responded less to phytohaemagglutinin (PHA) and concanavalin A (Con A) than MNC from the controls (P less than 0.001). In contrast, the responses of PNH MNC to poke weed mitogen (PWM) or lipopolysaccharide (LPS) were not impaired. MNC from a normal donor preincubated with anti-DAF became less responsive to PHA or Con A. We conclude that PNH lymphocytes show enhanced complement-susceptibility and that they are involved in their own expression of DAF as well as in other types of peripheral blood cells. The results of the responses to various lectins suggest the dysfunction of T cells in PNH.

Adult↗
PubMed1990

Neuropsychiatric disturbances in a patient with a nonmosaic isodicentric (X) (q21.32) chromosome.

A 41-year-old female patient with mental retardation and generalized epileptic seizure had a nonmosaic idic (X) (pter-q21.32::q21.32-pter) chromosome in peripheral lymphocytes and bone marrow cells. Primary amenorrhea, myelodysplastic syndrome, pigmented nevi and characteristic facial appearance were also observed. A few cases with the nonmosaic idic (X) (q::q) with various breakpoints reported previously commonly showed ovarian failure with dysfunction of relevant hormone. CNS abnormalities of the present case were demonstrated by CT, MRI and SPECT using 123I-IMP. CNS abnormalities were considered to be possibly due to karyotype with a nonmosaic idic (X) (q21.32).

Abnormalities, Multiple↗
PubMed1990

[3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in human frontal cortex: decreases in Alzheimer-type dementia.

We studied [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine [( 3H]TCP) binding to human frontal cortex obtained at autopsy from 10 histologically normal controls and eight histopathologically verified cases with Alzheimer-type dementia (ATD). Extensively washed membrane preparations were used to minimize the effects of endogenous substances. In ATD frontal cortex, the total concentration (Bmax) of [3H]TCP binding sites was significantly reduced by 40-50%. The apparent dissociation constant (KD) values showed no significant change. The reduction in binding capacity was also apparent in Triton X-100-treated membrane preparations, and there was a linear correlation between the number of [3H]TCP binding sites and that of N-methyl-D-aspartate (NMDA)-sensitive [3H]glutamate binding sites. [3H]TCP binding sites spared in ATD brains retained the affinity for the ligand and the reactivity to NMDA, L-glutamate, and glycine. These results suggest that the primary change in NMDA receptor-ion channel complex in ATD brains is the reduction of its number, possibly reflecting the loss of neurons bearing these receptor complexes, and that the functional linkage within the receptor complexes spared in ATD brains remains normal.

Alzheimer Disease↗
PubMed1990

Phosphoinositide breakdown in rat hippocampal slices: sensitivity to glutamate induced by in vitro anoxia.

We examined the effects of in vitro anoxia on phosphoinositide (PI) breakdown in rat hippocampal slices stimulated by glutamate and quisqualate. In addition to assays of accumulations of 3H-inositol phosphates (3H-IPs) degraded from prelabeled PI, we adopted direct assay procedures of inositol 1,4,5-triphosphate (1,4,5-IP3) using 1,4,5-IP3-specific binding protein to determine the formation of 1,4,5-IP3. The first effect, observed with anoxic incubation by itself, was the diminished quisqualate (10(-5) M)-stimulated accumulation of 3H-IPs degraded from prelabeled PI under prolonged anoxia. Quisqualate caused a transient increase in 1,4,5-IP3 formation in the early phase of anoxia, similar to that under oxygenated conditions. Glutamate (10(-5) M), under normal conditions, influenced neither the accumulation of 3H-IPs nor the formation of 1,4,5-IP3. Also, the accumulation of 3H-IPs under prolonged anoxia was unaffected. The same concentration of glutamate, however, gave rise to a transient increase in 1,4,5-IP3 content in the early phase of anoxia, similar to that caused by quisqualate. The second effect, observed by oxygenation following anoxia, was the induction of glutamate-stimulated accumulation of 3H-IPs. When the hippocampal slices were oxygenated following a sufficiently long (greater than 30-min) exposure to anoxia, glutamate (10(-5) M) caused a significant increase in accumulation of 3H-IPs degraded from prelabeled PI. Quisqualate-stimulated accumulation of 3H-IPs under oxygenated incubations was also increased by prior exposure of slices to anoxia. These results support the hypothesis that an exposure of hippocampal slices to anoxia induces a sensitivity of the PI breakdown pathway to glutamate and that, given an oxygen supply following sufficiently long exposure to anoxia, the slices maintain their sensitivity to glutamate with an apparent increase in the accumulation of 3H-IPs.

Animals↗
PubMed1990

[A case having initial onset of bronchial asthma, probably induced by prolonged mycoplasmal infection, accompanied with concurrent highly suspicious chlamydial infection].

A 37-year-old man who had had no allergic history was admitted to our hospital complaining of high fever, a dry hacking cough and dyspnea. Mycoplasma and Chlamydia mixed infection was diagnosed because of increased antibody titers to simultaneous Mycoplasma pneumoniae and Chlamydia psittaci, however only the Mycoplasma pneumoniae antibody titer was not decreased during the over six months. One month after the onset, bronchial asthma was diagnosed subsequently from for the clinical symptoms of wheeze and cough. Clinical studies of the dual infection and the possibility of Mycoplasma pneumoniae as the probable antigen of bronchial asthma were discussed.

Adult↗
PubMed1990

Effects of captopril on urinary excretion of albumin and prostaglandins in patients with diabetic nephropathy.

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

[Chronic myelomonocytic leukemia transformed from refractory anemia with ring sideroblasts with a rare abnormal chromosome, inv (12)].

We report here a rare transformation from refractory anemia with ring sideroblasts (RARS) to chronic myelomonocytic leukemia (CMML). A rare karyotype, inv (12), was also seen at the phase of CMML. A 76-year-old female consulted a physician because of hoarseness in June, 1983. An anemia was found and blood transfusions were made. In August, 1983, she was referred and admitted to Tsukuba University Hospital for a further examination of anemia. A diagnosis of MDS (RARS) was made by hematological examinations, and pyridoxamine was administered from September, 1983. The monocyte counts in the peripheral blood increased above 1,000/microliters continuously from June, 1985, and an exacerbation of anemia was also seen. At the second admission to our hospital in August, 1988, the diagnostic criteria for CMML by the FAB co-operative group was fulfilled. At that time, chromosomal analysis revealed an abnormal karyotype; 46XY, inv (12) (p13.3 q15). Even at the phase of CMML, ringed sideroblasts were also seen in 2.2% of nucleated cell count in the bone marrow. To our knowledge, only 12 cases have been reported as transformation from another type of MDS to CMML. The present case is thought to be a rare case of transformation of MDS. On the other hand, 8 cases with inv (12) associated with malignant hematological disorders have been reported previously. Four of the above 8 cases were MDS. A relationship between development of MDS and inv (12) was suggested.

Aged↗